Cyclodextrins in dental products

ABSTRACT

Oral rinse and dentifrice compositions, comprising a phenolic selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, triclosan, and mixtures thereof; and a cyclodextrin selected from the group consisting of hydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropyl γ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methyl β-cyclodextrin, and mixtures thereof. These compositions are useful in retarding the development of plaque, treating gingivitis, and in treating the presence of micro-organisms in the oral cavity.

BACKGROUND OF THE INVENTION

[0001] The present invention relates to dental products comprisingcyclodextrins.

[0002] Dental plaque is present to some degree, in the form of a film,on virtually all dental surfaces. It is a by-product of microbialgrowth, and comprises a dense microbial layer consisting of a mass ofmicro-organisms embedded in a polysaccharide matrix. The micro-organismspresent in plaque are mainly coccoidal organisms, particularly in earlyplaque. As plaque ages and matures, gram negative anaerobes andfilamentous organisms appear and become more common after a few days.Plaque itself adheres to dental surfaces and may not be removedcompletely even with a rigorous brushing regimen and can build up, forexample, in recessed areas of tooth surfaces, such as approximal regionsand fissures. Moreover, plaque rapidly reforms on the tooth surfaceafter it is removed.

[0003] Plaque may form on any part of the tooth surfaces, and can befound particularly at the gingival margin, in pits and fissures in theenamel, and on the surface of dental calculus. The danger associatedwith the formation of plaque on the teeth lies in the tendency of plaqueto build up and eventually contribute to gingivitis, periodontitis andother types of periodontal disease, as well as dental caries and dentalcalculus.

[0004] More specifically, dental plaque is a precursor to the formationof the hard crystalline build up on teeth referred to as dentalcalculus. Both the bacterial and the nonbacterial components of plaquemineralize to form calculus, which comprises mineralized bacteria aswell as organic constituents, such as epithelial cells, live bacteria,salivary proteins, leukocytes, and crystalline substances containingboth calcium and phosphorous, e.g., hydroxyapatite, Ca₁₀(PO₄)₆(OH)₂,octacalcium phosphate, Ca₈(HPO₄)₂(PO₄)_(4.)5H₂O, brushite, CaHPO₄.2H₂O,and whitlockite, which is considered to have the formula β-Ca₃(PO₄)₂.Dental plaque and, hence, calculus are particularly prone to form at thegingival margin, i.e., the junction of the tooth and gingiva. Thebuildup of plaque at, and below, the gingival margin is believed to bethe prime cause of gingivitis and periodontal disorders.

[0005] Mouthwashes have been formulated to contain antimicrobialingredients whose function is to reduce the buildup of plaque, either bythe direct bactericidal action (i.e. killing) on plaque and salivarymicro-organisms and by bacteriostatic action (i.e. growth inhibition) onplaque and salivary micro-organisms. Scheie, A. AA. (1989) Modes ofAction of Currently Known Chemical Anti-Plaque Agents Other thanChlorhexidine. J. Dent. Res. 68 Special Issue: 1609-1616. Oralcompositions including mouthwashes and dentifrices containing phenoliccompounds are referred to in U.S. Pat. Nos. 4,945,087; WO 94/16.16,674;WO 94/07477; and WO 94/18939. Oral composition including triclosan arereferred to in the following: U.S. Pat. Nos. 4,892,220; 5,032,386;5,037,637; 5,034,154; 5,080,887; 5,236,699; 5,043,154; 5,032,385; and5,156,835 as well as EPO 85303216.7.

[0006] However phenolics useful in oral compositions have low aqueoussolubilities which limit their use in oral compositions and they requirehigh levels of either 1) alcohol; 2) surfactants; or 3) co-solvents orcombinations of the above for sufficient solubility in the carrier. PCTAppln No. WO 94/16674.

[0007] For example, thymol has been used as a anthelmintic andantiseptic, in mouthwashes containing a combination of menthol, methylsalicylate, eucalyptol and thymol. However, these compositions arecharacterized by their relatively high alcohol levels which causes themto have negative aesthetics, including excessive “bite” and “burn.”

[0008] Triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether) is aphenolic, nonionic antimicrobial agent used in various soap and toiletryproducts. In the oral care area, triclosan has been used as aplaque-inhibitory agent in various toothpastes and mouthrinses.Triclosan is a broad-spectrum antimicrobial that has shown activity inin vitro assays. Regos, J. and Hitz, H. R. (1974) Investigation of Modeof Action of Triclosan, A Broad Spectrum Antimicrobial Agent. Zbl BaktHyg I Abt Orig A 226:390-401; Vischer, W. A. and Regos, J. (1974)Antimicrobial Spectrum of Triclosan, A Broad-Spectrum AntimicrobialAgent for Topical Application. Zbl Bakt Hyg I Agt Orig A 226:376-389,including chemostat studies; Bradshaw, D. J., Marsh, P. D., Watson, G.K. and Cummins, D. (1993) The Effects of Triclosan and Zinc Citrate,Alone and in Combination, on a Community of Oral Bacteria Grown invitro. J. Dent Res. 72:25-30; Herles, S., Olsen, S., Afflito, J. andGaffar, A. (1994) Chemostat Flow Cell System: An in vitro Model for theEvaluation of Antiplaque Agents. J. Dent Res. 73:1748-1755, as well asanimal tests; Nabi, N., Mukerjee, C., Schmid, R., Gaffar, A. (1989) InVitro and In Vivo Studies on Triclosan/PVM/MA copolymer/NaF Combinationas an Antiplaque Agent. Am. J. Dent. Spec Issue No. 2: 197-206; andhuman clinical studies; Garcia-Godoy, F., Garcia-Godoy, F., DeVizio, W.,Volpe, A. R., Ferlauto, R. J. and Miller, J. M. (1990) Effect of aTriclosan/Copolymer/Fluoride Dentifrice on Plaque Formation andGingivitis: A 7-month Clinical Study. Am. J. Dent. 3:S15-S26; Rustogi,K. N., Petrone, D. M., Singh, S. M., Volpe, A. R. and Tavss, E. (1990)Clinical Study of a Pre-brush and Triclosan/Copolymer Mouthrinse: Effecton Plaque Formation. Am. J. Dent. 3:S67-S69; and Saxton, C. A., Lane, R.M. and van der Ouderaa, F. (1987) The Effects of a Dentifrice Containinga Zinc Salt and a Non-cationic Antimicrobial Agent on Plaque andGingivitis. J. Clin. Periodontol. 57:555-561. Although triclosan whendelivered orally, is taken up by plaque and is moderately substantive,its bioactivity is limited by its poor aqueous solubility. Thus,triclosan has to be solubilized either by alcohol or surfactants such assodium lauryl sulfate when formulated into a conventional dentifrice ormouthrinse product. Kjaerheim, V., Waaler, S. M., Rolla, G. (1994)Significance of Choice of Solvents for the Clinical Effect ofTriclosan-containing Mouthrinses. Scand. J. Dent. Res. 102:202-205.

[0009] Cyclodextrins are known to form inclusion complexes with variouscompounds. The cyclodextrin molecule consists of glucopyranose unitsarranged in a torus-like or donut-like configuration having all thesecondary hydroxyl groups located on one side of the torus and allprimary hydroxyl groups located on the other side. Alpha, beta, andgamma cyclodextrin contain 6, 7 & 8 cyclic glucopyranose units,respectively, in the torus shell. The “lining” of the internal cavity isformed by hydrogen and glucosidic oxygen-bridge atoms and therefore thesurface is slightly apolar.

SUMMARY OF THE INVENTION

[0010] The present invention relates to an oral rinse composition,comprising:

[0011] a) from about 0.01% to about 2.5% by weight of a phenolic, saidphenolic selected from the group consisting of menthol, eucalyptol,methyl salicylate, thymol, triclosan, and mixtures thereof;

[0012] b) From about 0.1% by weight to about 25% by weight of acyclodextrin, said cyclodextrin selected from the group consisting ofhydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropylγ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methylβ-cyclodextrin, and mixtures thereof;

[0013] c) Up to about 25% by weight ethanol; and

[0014] d) an orally acceptable carrier.

[0015] The present invention also relates to a dentifrice in the form ofa toothpaste or tooth gel, comprising:

[0016] a) from about 0.01% to about 10% by weight of a phenolic, saidphenolic selected from the group consisting of menthol, eucalyptol,methyl salicylate, thymol, triclosan, and mixtures thereof;

[0017] b) From about 0.1% by weight to about 60% by weight of acyclodextrin, said cyclodextrin selected from the group consisting ofhydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropylγ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methylβ-cyclodextrin, and mixtures thereof;

[0018] c) up to about 60% by weight of an orally acceptable dentalabrasive, for example, silica, alumina, calcium pyrophosphate andcalcium carbonate; and

[0019] d) an orally acceptable carrier.

[0020] The present also relates to a method for retarding development ofplaque on a dental surface in the oral cavity of a mammal, comprisingadministering to said dental surface an amount of said oral rinsecomposition effective in retarding said development of plaque.

[0021] The present also relates to a method for retarding development ofplaque on a dental surface in the oral cavity of a mammal, comprisingadministering to said dental surface an amount of said dentifriceeffective in retarding said development of plaque.

[0022] The present also relates to a method of treating gingivitis,comprising administering to a mammal in need of such treatment an amountof said oral rinse composition effective in treating gingivitis.

[0023] The present also relates to a method of treating gingivitis,comprising administering to a mammal in need of such treatment an amountof said dentifrice effective in treating gingivitis.

[0024] The present also relates to a method of treating the presence ofmicro-organisms in the oral cavity of a mammal, comprising administeringto the mammal in need of such treatment an amount of said oral rinsecomposition effective in reducing the viable population of saidmicro-organisms.

[0025] The present also relates to a method of treating the presence ofmicro-organisms in the oral cavity of a mammal, comprising administeringto the mammal in need of such treatment an amount of said dentifriceeffective in reducing the viable population of said micro-organisms.

DETAINED DESCRIPTION OF THE INVENTION

[0026] Compositions of the present invention include low-alcohol oralcare .compositions that contain cyclodextrin compounds which solubilizephenolic antimicrobial compounds. As a result of higher levels ofsolubilized phenolics in a solution, the phenolic compounds haveimproved bioavailability in treating plaque, as well as providingcompositions having excellent low-temperature stability. Thesecompositions retard the development of plaque as well as treatgingivitis and periodontal diseases without the use of high alcohollevels, high surfactant levels or the use of other co-solvents.

[0027] Phenolics useful as antimicrobials in the present invention andeffective in treating micro-organisms present in the oral cavity of amammal include menthol, methyl salicylate, eucalyptol, thymol andtriclosan. Thymol and triclosan are generally considered to have thebest antimicrobial activity of these phenolics. For oral rinses,phenolic compounds or mixtures thereof preferably range from about 0.01%by weight to about 0.5% by weight, more preferably from about 0.05% byweight to about 0.3% by weight. For dentifrices, the amount of phenoliccompounds or a mixture thereof preferably range from about 0.01% byweight to about 5% by weight, more preferably from about 0.25% by weightto about 3% by weight.

[0028] Molecules, or functional groups of molecules having moleculardimensions that match the cyclodextrin cavity, being less hydrophilic(i.e. more hydrophobic) than water, will position themselves in thecyclodextrin cavity at the expense of water molecules. In aqueoussolutions, the slightly apolar cyclodextrin cavity is occupied by watermolecules which are energetically unfavored (polar-apolar interaction)and are therefore readily substituted by appropriate “guest molecules”which are less polar than water. In the case of the present invention,the “guest molecules” are the phenolic ingredients mentioned above.

[0029] Suitable cyclodextrins useful in the present invention includehydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropylγ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin and methylβ-cyclodextrin. Suitable candidate cyclodextrins typically have to havean aqueous solubility of at least about 10% by weight and formsufficiently soluble phenolic-cyclodextrin complexes to be suitable forthis invention. Hydroxypropyl β-cyclodextrin is the preferredcyclodextrin.

[0030] Each of the seven cyclic glucopyranose units in β-cyclodextrincontains three hydroxyl groups in the 2-,3- and 6-positions, which canbe etherified. In the case of the partially etherified cyclodextrinderivatives used in this invention, only some of these positions aresubstituted with hydroxyethyl or hydroxypropyl groups. A wide range ofsubstitutions can be made per molecule up to a maximum of 18. Thepreferred range of substitution ranges from about 0.5 to 8 positions.Thus, hydroxypropyl β-cyclodextrin is a chemically modified cyclodextrinconsisting of an amorphous isomeric mixture of thousands of geometricand optical isomers with varying degrees of substitution and varyingnumbers of hydroxypropyl substituents, however the size of thecyclodextrin cavity is constant for these isomers.

[0031] For oral rinses, these amount of soluble cyclodextrin ranges fromabout 0.1% by weight to about 25% by weight, preferably from about 0.5%by weight to about 20% by weight, more preferably from about 1% byweight to about 5% by weight, selected from the group consisting ofhydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropylγ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methylβ-cyclodextrin, and mixtures thereof are useful for the invention. Fordentifrices, the amount of soluble cyclodextrin ranges from about 0.1%by weight to about 60% by weight, preferably from about 5% by weight toabout 30% by weight selected from the group consisting of hydroxypropylβ-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropylγ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methylβ-cyclodextrin, and mixtures thereof are useful for the invention.

[0032] For dentifrice compositions suitable abrasives includeprecipitated silica or silica gels which have an average particle sizeranging from about 0.1 to about 50 microns. Preferred silica abrasivesinclude those marketed under the tradename “Sylodent®” or “Syloid®” bythe W. R. Grace & Co. and those marketed under the tradename “Zeodent®”by the J. M. Huber Corp. Other suitable abrasives, having a suitableparticle size as described above, include β-phase calcium pyrophosphate,alumina and calcium carbonate. The amount of abrasive in a dentifricecomposition ranges up to about 60% by weight, preferably from 10% byweight to 40% by weight.

[0033] Dentifrice and oral rinse compositions also may contain asuitable fluoride source. Typical sources include soluble salts of thefluoride ion; e.g. sodium fluoride, potassium fluoride, stannousfluoride, stannous fluorozirconate etc.; or, soluble salts of themonofluorophosphate ion; e.g. sodium monofluorophosphate etc. Thepreferred fluoride source is sodium fluoride. The fluoride ion sourceshould be sufficient to provide from about 50 ppm to about 2,500 ppmfluoride, preferably from about 250 ppm to about 1500 ppm fordentifrices and from about 50 ppm to about 250 ppm fluoride for oralrinses.

[0034] A liquid carrier generally includes mixtures of water and ethanolfor oral rinses, although the carrier can be alcohol-free, especially indentifrices. For oral rinses, the amount of water ranges upwards fromabout 25% by weight. The amount of alcohol ranges by weight from about0% to about 25% by weight, preferably from about 0% by weight to about15% by weight. For dentifrices, the amount of water ranges from about 0%by weight to about 60% by weight, preferably from about 0% by weight toabout 40% by weight.

[0035] The pH of the oral rinses and dentifrice compositions can rangefrom about 3.5 to about 8.5.

[0036] The oral rinse compositions, for example, Examples 1 to 5, areunusually stable so as to be substantially clear and substantially freeof precipitation, flocculation, or crystal formation at about roomtemperature (about 25° C.) as well as at low temperatures of at leastabout 5° C. for at least about 1 week. The low temperature stability ofthese compositions is determined by cooling the compositions to about 5°C., storing for at least seven days and determining whether anyprecipitate, crystallized or flocculated material is formed in the clearcompositions (solutions and gels).

[0037] Oral surfactants useful in the present invention include nonionicand anionic surfactants. Oral surfactants employed include blockco-polymers of polyoxyethylene and polyoxypropylene such as thePluronics from BASF. Other oral surfactants include soluble alkylsulfonates having 10 to 18 carbon atoms, such as sodium lauryl sulfate,and sulfates of monoglycerides of fatty acids having 10 to 18 carbonatoms or sarcosinates (including salts and derivatives) such assodium-N-lauroyl sarcosinate. Mixtures of anionic and nonionicsurfactants can be used. These ingredients are generally present fromabout 0% by weight to about 4% by weight, preferably from about 0% byweight to about 1% by weight for oral rinses and from about 0.5% byweight to about 4% by weight for dentifrices.

[0038] Additional antiplaque agents can also be optionally added to thecompositions. These include cetyl pyridinium chloride and relatedquaternary salts, chlorhexidine, zinc salts such as zinc chloride,stannous salts such as stannous chloride or stannous fluoride andperoxygens such as hydrogen peroxide and carbamide peroxide. Theseoptional antiplaque agents are generally present at levels ranging formabout 0% to about 5% by weight.

[0039] Additional anticalculus agents can be optionally added to thecompositions. These include tetra-alkali or di-alkali metalpyrophosphate salts and zinc salts, such as, but not limited to, zincchloride etc. These optional anticalculus agents are generally presentat levels ranging from about 0% by weight to about 10% by weight forpyrophosphate salts and from about 0% by weight to about 3% by weightfor zinc salts.

[0040] In compositions relating to the invention, preservatives may beused, especially for non-alcohol or low alcohol compositions. Theseinclude benzoic acid, sodium benzoate, methylparaben, propylparaben,sorbic acid and potassium sorbate. These optional preservative agentsare generally present at levels ranging from about 0% by weight to about2% by weight.

[0041] In compositions relating to the invention, buffering systems maybe used to stabilize the pH in the product. Typical buffering systemsinclude, but are not limited to, citrate, benzoate, gluconate andphosphate. Buffering systems are present in concentrations from about0.01% by weight to about 1% by weight.

[0042] In addition to the above ingredients, the invention may includeother optional ingredients to impart desired mouth feel and provideflavoring and coloring.

[0043] Humectants are an optional component of the compositions. Fororal rinses they impart a moist and elegant feel to the mouth and intoothpaste compositions they prevent hardening on exposure to air. Somehumectants can provide sweetness to the composition. Suitable humectantsinclude edible polyhydric alcohols such as glycerin, sorbitol, propyleneglycol and xylitol. The humectant generally is present in an amountranging from 0% by weight to 30% by weight for oral rinses and 0% byweight to 70% by weight for dentifrice compositions.

[0044] Thickening agents or binders are an optional component of thecompositions. Typical thickening include, xanthan gum, carrageenan,carboxyvinyl polymers, carbomers, cellulose gums such as carboxymethylcellulose, cellulose derivatives such as hydroxyethylcellulose andsilicas. Thickeners are usually present in the compositions from about0% by weight to 2% by weight. Xanthan gum is the preferred thickener inoral rinses. In dentifrices, silica-based thickeners can be used atconcentrations from 0% by weight to about 20% by weight. “Sylox®” by W.R. Grace & Co. is the tradename of the preferred silica-based thickener.

[0045] Flavoring agents can be added to the compositions. The flavorantmay be a flavoring oil or mixture of flavoring oils such as oil ofpeppermint, spearmint, wintergreen, clove, sassafras, lemon, orange orlime. Sweetening agents such as saccharin, lactose, maltose, aspartame,sodium cyclamate, polydextrose etc. can be added to the compositions.Flavoring agents generally are present in an amount ranging from 0.001%by weight to about 0.5% by weight for oral rinses and 0.25% by weight toabout 5% by weight for dentifrice compositions. Sweetening agentsgenerally are present in an amount ranging from 0.001% by weight toabout 5% by weight for oral rinse and dentifrice compositions. Coloringagents generally are present in an amount ranging from 0% by weight to0.01% by weight.

EXAMPLE 1

[0046] A dental rinse was formulated by adding Hydroxypropylβ-cyclodextrin and poloxamer to water using a Master Servodyne® mixerwith high-lift blade rotating at 200-300 rpm to give a clear aqueoussolution. Benzoic acid, thymol, menthol, eucalyptol, methyl salicylateand flavor were added with stirring to give a clear solution. Sodiumcitrate, citric acid, dye, sorbitol and sodium saccharin were then addedwith continual stirring to give a clear solution. The resulting clearblue-green product was mixed for a further 30 minutes. The product had apH of approximately 4.0. Ingredient Weight Percent poloxamer 407 0.50sodium citrate 0.04 citric acid 0.01 sorbitol 70% 22.00 FD + C green no.3 0.0006 hydroxypropyl β-cyclodextrin 5.00 sodium saccharin 0.05 benzoicacid 0.15 thymol 0.064 eucalyptol 0.092 menthol 0.042 methyl salicylate0.060 flavor 0.10 purified water 71.8914 total 100.0000

EXAMPLE 2

[0047] A dental rinse was formulated by adding poloxamer, sodiumcitrate, citric acid, sodium saccharin, hydroxypropyl β-cyclodextrin,sorbitol and dye to water, at room temperature, using a MasterServodyne® mixer with high-lift blade rotating at 200-300 rpm to give aclear aqueous solution. Benzoic acid, menthol, thymol, methylsalicylate, eucalyptol and flavor were added to the 190° alcohol to givea clear alcoholic solution. The alcoholic phase was added slowly to theaqueous phase which was continually agitated until the addition wascomplete. The resulting clear blue-green product was mixed for a further30 minutes. The product had a pH of approximately 4.0. Ingredient WeightPercent poloxamer 407 0.50 sodium citrate 0.04 citric acid 0.01 sorbitol70% 22.00 FD + C green no. 3 0.0006 hydroxypropyl β-cyclodextrin 1.0sodium saccharin 0.05 alcohol 190 proof 12.00 benzoic acid 0.15 thymol0.064 eucalyptol 0.092 menthol 0.042 methyl salicylate 0.060 flavor 0.10purified water 63.8914 total 100.0000

EXAMPLE 3

[0048] A dental rinse was formulated by adding poloxamer, sodiumcitrate, citric acid, sodium saccharin, hydroxypropyl β-cyclodextrin,sorbitol and dye to water using a Master Servodyne® mixer with high-liftblade rotating at 200-300 rpm to give a clear aqueous solution. Benzoicacid, triclosan (Irgacare MP—Ciba Geigy) and flavor were added to the190° alcohol to give a clear alcoholic solution. The alcoholic phase wasadded slowly to the aqueous phase which was continually agitated untilthe addition was complete. The resulting clear blue-green product wasmixed for a further 30 minutes. The product had a pH of approximately4.0. Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006hydroxypropyl β-cyclodextrin 2.50 sodium saccharin 0.05 alcohol 190proof 8.00 benzoic acid 0.15 triclosan 0.10 flavor 0.10 purified water66.5494 total 100.0000

EXAMPLE 4

[0049] A dental rinse was formulated by adding poloxamer, sodiumcitrate, citric acid, sodium saccharin, hydroxypropyl β-cyclodextrin,sorbitol and dye to water, at room temperature, using a MasterServodyne® mixer with high-lift blade rotating at 200-300 rpm to give aclear aqueous solution. Benzoic acid, menthol, thymol, methylsalicylate, eucalyptol and flavor were added to the 190° alcohol to givea clear alcoholic solution. The alcoholic phase was added slowly to theaqueous phase which was continually agitated until the addition wascomplete. The resulting clear blue-green product was mixed for a further30 minutes. The product had a pH of approximately 4.0. Ingredient WeightPercent poloxamer 407 0.50 sodium citrate 0.04 citric acid 0.01 sorbitol70% 22.00 FD + C green no. 3 0.0006 hydroxypropyl β-cyclodextrin 1.25sodium saccharin 0.05 alcohol 190 proof 8.00 benzoic acid 0.15 thymol0.064 eucalyptol 0.092 menthol 0.042 methyl salicylate 0.060 flavor 0.10purified water 67.6414 total 100.0000

EXAMPLE 5

[0050] A dental rinse was formulated by adding poloxamer, sodiumcitrate, citric acid, sodium saccharin, hydroxypropyl β-cyclodextrin,zinc chloride, sorbitol and dye to water using a Master Servodyne® mixerwith high-lift blade rotating at 200-300 rpm to give a clear aqueoussolution. Benzoic acid, menthol, thymol, methyl salicylate, eucalyptoland flavor were added to the 190° alcohol to give a clear alcoholicsolution. The alcoholic phase was added slowly to the aqueous phasewhich was continually agitated until the addition was complete. Theresulting clear blue-green product was mixed for a further 30 minutes.The product had a pH of approximately 4.0. Ingredient Weight Percentpoloxamer 407 0.50 sodium citrate 0.04 citric acid 0.01 sorbitol 70%22.00 FD + C green no. 3 0.0006 hydroxypropyl β-cyclodextrin 1.25 zincchloride 0.10 sodium saccharin 0.03 alcohol 190 proof 8.00 benzoic acid0.15 thymol 0.064 eucalyptol 0.092 menthol 0.042 methyl salicylate 0.060flavor 0.10 purified water 67.5614 total 100.0000

EXAMPLE 6

[0051] A gel dentifrice was formulated by dispersing carboxymethylcellulose in the glycerin and polyethylene glycol using a Lighteningmixer. NaF was dissolved separately in the water. Water and sorbitolwere added and mixed for 25 minutes sodium saccharin and hydroxypropylβ-cyclodextrin were then added and mixed for a further 10 minutes. Thephenolics were mixed together, i.e. eucalyptol, methyl salicylate,thymol and menthol, to make a phenolic phase. The phenolic phase wasadded to the cellulose/sorbitol/cyclodextrin/water phase until thephenolics are dissolved. Sylodent® 700, Sylox® 2, FD+C Blue No. 1 andsodium lauryl sulfate were then added and mixed thoroughly for 30minutes. The resulting clear blue gel was deaerated to remove airbubbles. Ingredient Weight Percent glycerin 14.000 sorbitol, 70% 27.343carboxymethyl cellulose, 9M8 0.900 polyethylene glycol, PEG-8 3.000purified water 13.429 FD + C blue no. 1 0.005 hydroxypropylβ-cyclodextrin 15.000 sodium saccharin 0.500 NaF 0.243 Sylodent ® 70014.000 Sylox ® 2 8.000 thymol 0.640 eucalyptol 0.920 menthol 0.420methyl salicylate 0.600 sodium lauryl sulfate 1.000

1. A stable oral rinse composition, comprising: a) from about 0.01% to about 2.5% by weight of a phenolic, said phenolic selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, triclosan, and mixtures thereof; b) from about 0.1% by weight to about 25% by weight of a cyclodextrin, said soluble cyclodextrin selected from the group consisting of hydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropyl γ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methyl β-cyclodextrin, and mixtures thereof; c) up to about 25% by weight ethanol; and d) an orally acceptable carrier.
 2. A stable oral rinse composition according to claim 1, wherein the amount of cyclodextrin is from about 1% by weight to about 5% by weight.
 3. A stable oral rinse composition according to claim 1, wherein the amount of ethanol is up to about 15% by weight.
 4. A stable oral rinse composition according to claim 1, further including up to about 4% by weight of an orally acceptable surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant, or mixtures thereof.
 5. A stable oral rinse composition according to claim 4, wherein the amount of orally acceptable surfactant is up to about 1% by weight.
 6. A stable oral rinse composition according to claim 1, further including up to about 5% by weight of an orally acceptable antiplaque agent.
 7. A stable oral rinse composition according to claim 6, wherein the orally acceptable antiplaque agent is selected from the group consisting of cetyl pyridinium chloride, cetyl pyridinium chloride related quaternary pharmaceutically acceptable salts, chlorhexidine, zinc pharmaceutically acceptable salts, stannous pharmaceutically acceptable salts and pharmaceutically acceptable peroxygens.
 8. A stable oral rinse composition according to claim 1, further including an orally acceptable anticalculus agent.
 9. A stable oral rinse composition according to claim 8, wherein the orally acceptable anticalculus agent includes up to about 10% by weight of a pyrophosphate pharmaceutically acceptable salt.
 10. A stable oral rinse composition according to claim 1, further including an orally acceptable suitable fluoride ion source sufficient to provide from about 50 ppm to about 2500 ppm fluoride.
 11. A stable oral rinse composition according to claim 10, wherein the amount of the orally acceptable suitable fluoride ion source provides from about 50 ppm to about 250 ppm fluoride.
 12. A dentifrice in the form of a toothpaste or tooth gel, comprising: a) from about 0.01% to about 10% by weight of a phenolic, said phenolic selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, triclosan, and mixtures thereof; b) from about 0.1% by weight to about 60% by weight of a cyclodextrin, said cyclodextrin selected from the group consisting of hydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropyl γ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin and methyl β-cyclodextrin, and mixtures thereof; c) up to about 60% by weight of an orally acceptable dental abrasive; and d) an orally acceptable carrier.
 13. A dentifrice according to claim 12, wherein the amount of cyclodextrin is from about 5% by weight to about 30% by weight.
 14. A dentifrice according to claim 12, further including up to about 4% by weight of an orally acceptable surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant, or mixtures thereof.
 15. A dentifrice according to claim 14, wherein the amount of orally acceptable surfactant is from about 0.5% by weight to about 4% by weight.
 16. A dentifrice according to claim 12, further including up to about 5% by weight of an orally acceptable antiplaque agent.
 17. A dentifrice according to claim 16, wherein the orally acceptable antiplaque agent is selected from the group consisting of cetyl pyridinium chloride, cetyl pyridinium chloride related quaternary pharmaceutically acceptable salts, chlorhexidine, zinc pharmaceutically acceptable salts, stannous pharmaceutically acceptable salts and pharmaceutically acceptable peroxygens.
 18. A dentifrice according to claim 12, further including an orally acceptable anticalculus agent.
 19. A dentifrice according to claim 18, wherein the orally acceptable anticalculus agent includes up to about 10% by weight of a pyrophosphate pharmaceutically acceptable salt.
 20. A dentifrice according to claim 12, wherein the amount of orally acceptable dental abrasive is from about 10% by weight to about 40% by weight.
 21. A dentifrice according to claim 12, wherein the orally acceptable dental abrasive selected from the group consisting of silica, alumina, calcium pyrophosphate and calcium carbonate.
 22. A dentifrice according to claim 12, further including an orally acceptable suitable fluoride ion source sufficient to provide from about 50 ppm to about 2500 ppm fluoride.
 23. A dentifrice according to claim 22, wherein the amount of the orally acceptable suitable fluoride ion source sufficient to provide from about 250 ppm to about 1500 ppm fluoride.
 24. A stable oral rinse composition, comprising: a) from about 0.01% to about 0.5% by weight of a phenolic, said phenolic selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, triclosan, and mixtures thereof; b) from about 0.1% by weight to about 5% by weight of a cyclodextrin, said soluble cyclodextrin selected from the group consisting of hydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropyl γ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin, methyl β-cyclodextrin, and mixtures thereof; c) up to about 15% by weight ethanol; and d) up to about 1% by weight of an orally acceptable surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant, or mixtures thereof; and d) an orally acceptable carrier.
 25. A dentifrice in the form of a toothpaste or tooth gel, comprising: a) from about 0.01% to about 3% by weight of a phenolic, said phenolic selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, triclosan, and mixtures thereof; b) from about 0.1% by weight to about 30% by weight of a cyclodextrin, said cyclodextrin selected from the group consisting of hydroxypropyl β-cyclodextrin, hydroxyethyl β-cyclodextrin, hydroxypropyl γ-cyclodextrin, hydroxyethyl γ-cyclodextrin, α-cyclodextrin and methyl β-cyclodextrin, and mixtures thereof; c) up to about 40% by weight of an orally acceptable dental abrasive; d) up to about 4% by weight of an orally acceptable surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant, or mixtures thereof; e) an orally acceptable suitable fluoride ion source sufficient to provide from about 250 ppm to about 1500 ppm fluoride; and f) an orally acceptable carrier.
 26. A method for retarding development of plaque on a dental surface in the oral cavity of a mammal, comprising administering to said dental surface an amount of a composition according to claim 1 effective in retarding said development of plaque.
 27. A method for retarding development of plaque on a dental surface in the oral cavity of a mammal, comprising administering to said dental surface an amount of a dentifrice according to claim 12 effective in retarding said development of plaque.
 28. A method of treating gingivitis, comprising administering to a mammal in need of such treatment an amount of a composition according to claim 1 effective in treating gingivitis.
 29. A method of treating gingivitis, comprising administering to a mammal in need of such treatment an amount of a dentifrice according to claim 12 effective in treating gingivitis.
 30. A method of treating the presence of micro-organisms in the oral cavity of a mammal, comprising administering to the mammal in need of such treatment an amount of a composition according to claim 1 effective in reducing the viable population of said micro-organisms.
 31. A method of treating the presence of micro-organisms in the oral cavity of a mammal, comprising administering to the mammal in need of such treatment an amount of a dentifrice according to claim 12 effective in reducing the viable population of said micro-organisms. 